Multi-walled carbon nanotubes functionalized with recombinant Dengue virus 3 envelope proteins induce significant and specific immune responses in mice

Alice F. Versiani, Ruiz G. Astigarraga, Eliseu S.O. Rocha, Ana Paula M. Barboza, Erna G. Kroon, Milene A. Rachid, Daniele G. Souza, Luiz O. Ladeira, Edel F. Barbosa-Stancioli, Ado Jorio, Flávio G. Da Fonseca

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Dengue is the most prevalent arthropod-borne viral disease in the world. In this article we present results on the development, characterization and immunogenic evaluation of an alternative vaccine candidate against Dengue. Methods: The MWNT-DENV3E nanoconjugate was developed by covalent functionalization of carboxylated multi-walled carbon nanotubes (MWNT) with recombinant dengue envelope (DENV3E) proteins. The recombinant antigens were bound to the MWNT using a diimide-activated amidation process and the immunogen was characterized by TEM, AFM and Raman Spectroscopy. Furthermore, the immunogenicity of this vaccine candidate was evaluated in a murine model. Results: Immunization with MWNT-DENV3E induced comparable IgG responses in relation to the immunization with non-conjugated proteins; however, the inoculation of the nanoconjugate into mice generated higher titers of neutralizing antibodies. Cell-mediated responses were also evaluated, and higher dengue-specific splenocyte proliferation was observed in cell cultures derived from mice immunized with MWNT-DENV3E when compared to animals immunized with the non-conjugated DENV3E. Conclusions: Despite the recent licensure of the CYD-TDV dengue vaccine in some countries, results from the vaccine's phase III trial have cast doubts about its overall efficacy and global applicability. While questions about the effectiveness of the CYD-TDV vaccine still lingers, it is wise to keep at hand an array of vaccine candidates, including alternative non-classical approaches like the one presented here.

Original languageEnglish (US)
Article number26
JournalJournal of Nanobiotechnology
Volume15
Issue number1
DOIs
StatePublished - Apr 4 2017
Externally publishedYes

Keywords

  • Carbon nanotubes
  • Dengue vaccine
  • Nanoconjugate
  • Subunit vaccine

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Applied Microbiology and Biotechnology
  • Pharmaceutical Science

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